Systematic review of gut microbiota composition, metabolic alterations, and the effects of treatments on PCOS and gut microbiota across human and animal studies

Abstract

Introduction: Polycystic ovary syndrome (PCOS) is an endocrine disorder affecting around 12% of women globally, associated with infertility and various comorbidities. Emerging evidence suggests a crucial role of gut microbiota in PCOS pathophysiology, prompting research to investigate alterations in gut microbial composition in patients with PCOS.

Methods: This systematic review aims to analyze human and animal studies that compare gut microbiota composition, gut-derived metabolites, and treatment interventions in PCOS patients versus healthy controls. A comprehensive literature search was conducted using PubMed, Scopus, and Web of Science, yielding studies examining gut microbiota, metabolomic shifts, and treatment responses in PCOS models and human populations.

Results: Our analysis revealed decreases in alpha diversity in PCOS patients, with more pronounced changes in beta diversity in animal models. Specific bacterial taxa, such as Bacteroides vulgatus, Escherichia-Shigella and Lactobacillus, showed implication in PCOS pathogenesis, suggesting potential microbial markers. Furthermore, discrepancies between human and animal studies show the need for humanized mouse models to bridge this gap. Interventions like probiotics and fecal microbiota transplantation (FMT) showed varying levels of efficacy, with FMT emerging as a more promising but invasive option, offering live bacteriotherapy as a potential therapeutic alternative. Alterations in gut-derived metabolites, including short-chain fatty acids and bile acids, highlighted the multifaceted nature of PCOS, with implications extending to metabolic, hormonal, and gut-brain axis disruptions.

Discussion: In conclusion, PCOS exhibits complex interactions between gut microbiota and metabolic pathways, necessitating further research with standardized methods and larger sample sizes to elucidate the microbiome's role in PCOS.

Keywords: endocrine system diseases; fecal microbiota transplantation; gastrointestinal microbiome; metabolomics; metagenomics; polycystic ovary syndrome.

Figure 1

PRISMA flow diagram. This figure was adapted from PRISMA 2020 flow diagram for new systematic reviews which included searches of databases and registers only (source: Page et al., 2021). This work is licensed under CC BY 4.0. To view a copy of this license, visit https://creativecommons.org/licenses/by/4.0/.

Figure 2

Gut microbiota alterations in PCOS patients. Grid table showing gut microbiome diversity and taxa alterations in PCOS Patients compared to healthy controls. Red colors show significant decreases in PCOS patients, green significant increases, black no significant change, yellow significant change.

Figure 3

Gut microbiota alterations in PCOS animal models. Grid table showing gut microbiome diversity and taxa alterations in PCOS animal models compared to controls. Red colors show significant decreases in PCOS patients, green significant increases, black no significant change, yellow significant change, and gray no mention.

Figure 4

Gut microbiota and PCOS symptoms alterations post-treatment in PCOS patients. (A) Grid table showing gut microbiome diversity and taxa alterations in PCOS Patients Post-Treatment. Red colors show significant decreases post-treatment, green significant increases, black no significant change, yellow significant change, and gray no mention. (B) Grid table showing alterations in PCOS Symptoms Post-Treatment. Red colors show significant decreases post-treatment, green significant increases, black no significant change, yellow significant change, and gray no mention. Studies highlighted in orange are focused on pre/probiotic therapy.

Figure 5

Gut microbiota and PCOS symptoms alterations post-treatment in PCOS animal models. (A) Grid table showing gut microbiome diversity and taxa alterations in PCOS models post-treatment. Red colors show significant decreases post-treatment, green significant increases, black no significant change, yellow significant change, and gray no mention. Highlighted in blue are studies working on FMT. (B) Grid table showing alterations in PCOS Symptoms Post-Treatment. Red colors show significant decreases post-treatment, green significant increases, black no significant change, yellow significant change, and gray no mention. Studies highlighted in blue are focused FMT.

Figure 6

Gut metabolome alterations in PCOS patients. Grid table showing gut microbiome derived metabolites alterations in PCOS Patients compared to healthy controls, as well as post-treatment. Red colors show significant decreases in PCOS patients, green significant increases, Pink significant decrease post-treatment and blue significant increase post-treatment. If study has both PCOS patients and post-treatment results, only post-treatment is highlighted.

Figure 7

Gut metabolome alterations in PCOS animal models. Grid table showing gut microbiome derived metabolites alterations in PCOS models compared to controls, as well as post-treatment. Red colors show significant decreases in PCOS models, green significant increases, Pink significant decrease post-treatment and blue significant increase post-treatment. If study has both PCOS models and post-treatment results, only post-treatment is highlighted.